JP4782344B2 - ベンザゾール誘導体と、そのｊｎｋモジュレータとしての利用法 - Google Patents

Info

Publication number

JP4782344B2

JP4782344B2 JP2001549390A JP2001549390A JP4782344B2 JP 4782344 B2 JP4782344 B2 JP 4782344B2 JP 2001549390 A JP2001549390 A JP 2001549390A JP 2001549390 A JP2001549390 A JP 2001549390A JP 4782344 B2 JP4782344 B2 JP 4782344B2

Authority

JP

Japan

Prior art keywords

substituted

unsubstituted

benzothiazol

acetonitrile

group

Prior art date

1999-12-24

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired - Lifetime

Links

• Espacenet
• Global Dossier
• Discuss

• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title claims description 66
• -1 nitro, sulfoxy, sulfonyl Chemical group 0.000 claims description 138
• 125000001072 heteroaryl group Chemical group 0.000 claims description 62
• 229910052739 hydrogen Inorganic materials 0.000 claims description 55
• 239000001257 hydrogen Substances 0.000 claims description 43
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 42
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 40
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 39
• 125000000217 alkyl group Chemical group 0.000 claims description 39
• 125000003118 aryl group Chemical group 0.000 claims description 37
• 150000002431 hydrogen Chemical class 0.000 claims description 35
• 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 claims description 33
• WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 33
• 150000003839 salts Chemical class 0.000 claims description 32
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 31
• 229910052736 halogen Inorganic materials 0.000 claims description 30
• 150000002367 halogens Chemical class 0.000 claims description 29
• 125000003107 substituted aryl group Chemical group 0.000 claims description 28
• 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 27
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 26
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 26
• 201000010099 disease Diseases 0.000 claims description 26
• 238000000034 method Methods 0.000 claims description 25
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 24
• 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 23
• 125000001302 tertiary amino group Chemical group 0.000 claims description 23
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 21
• 239000008194 pharmaceutical composition Substances 0.000 claims description 21
• 125000003545 alkoxy group Chemical group 0.000 claims description 20
• 125000005309 thioalkoxy group Chemical group 0.000 claims description 20
• 125000001424 substituent group Chemical group 0.000 claims description 19
• 239000000126 substance Substances 0.000 claims description 16
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
• 125000002252 acyl group Chemical group 0.000 claims description 14
• 125000004442 acylamino group Chemical group 0.000 claims description 14
• 125000004423 acyloxy group Chemical group 0.000 claims description 14
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 14
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 14
• 125000004953 trihalomethyl group Chemical group 0.000 claims description 14
• 230000000694 effects Effects 0.000 claims description 13
• 125000001453 quaternary ammonium group Chemical group 0.000 claims description 13
• 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 12
• 238000006243 chemical reaction Methods 0.000 claims description 12
• 238000002360 preparation method Methods 0.000 claims description 12
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 11
• 239000002585 base Substances 0.000 claims description 11
• 229910052717 sulfur Inorganic materials 0.000 claims description 10
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
• 229910052760 oxygen Inorganic materials 0.000 claims description 8
• 229940124530 sulfonamide Drugs 0.000 claims description 8
• 150000003456 sulfonamides Chemical class 0.000 claims description 8
• 239000003085 diluting agent Substances 0.000 claims description 7
• 239000003814 drug Substances 0.000 claims description 7
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 6
• 239000000654 additive Substances 0.000 claims description 6
• 125000000304 alkynyl group Chemical group 0.000 claims description 6
• 230000014509 gene expression Effects 0.000 claims description 6
• 150000003230 pyrimidines Chemical class 0.000 claims description 6
• 206010040070 Septic Shock Diseases 0.000 claims description 5
• PKNYJVSQHRVGTB-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-(2-methoxypyrimidin-4-yl)acetonitrile Chemical compound COC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 PKNYJVSQHRVGTB-UHFFFAOYSA-N 0.000 claims description 4
• HHPADGYFHUJULV-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(3-pyrazol-1-ylpropylamino)pyrimidin-4-yl]acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1NCCCN1C=CC=N1 HHPADGYFHUJULV-UHFFFAOYSA-N 0.000 claims description 4
• FDPMHJTUFOTVTN-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-[[3-(trifluoromethyl)pyridin-2-yl]amino]ethylamino]pyrimidin-4-yl]acetonitrile Chemical compound FC(F)(F)C1=CC=CN=C1NCCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 FDPMHJTUFOTVTN-UHFFFAOYSA-N 0.000 claims description 4
• OSXMTIFMYHFUHI-UHFFFAOYSA-N 4-[2-[[4-[1,3-benzothiazol-2-yl(cyano)methyl]pyrimidin-2-yl]amino]ethyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 OSXMTIFMYHFUHI-UHFFFAOYSA-N 0.000 claims description 4
• 208000023275 Autoimmune disease Diseases 0.000 claims description 4
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
• 125000002883 imidazolyl group Chemical group 0.000 claims description 4
• 125000004076 pyridyl group Chemical group 0.000 claims description 4
• 230000036303 septic shock Effects 0.000 claims description 4
• 208000024827 Alzheimer disease Diseases 0.000 claims description 3
• 206010003210 Arteriosclerosis Diseases 0.000 claims description 3
• 201000006474 Brain Ischemia Diseases 0.000 claims description 3
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
• 206010008120 Cerebral ischaemia Diseases 0.000 claims description 3
• 206010019196 Head injury Diseases 0.000 claims description 3
• 208000023105 Huntington disease Diseases 0.000 claims description 3
• 208000007201 Myocardial reperfusion injury Diseases 0.000 claims description 3
• 206010028980 Neoplasm Diseases 0.000 claims description 3
• 208000012902 Nervous system disease Diseases 0.000 claims description 3
• 208000017442 Retinal disease Diseases 0.000 claims description 3
• 208000006011 Stroke Diseases 0.000 claims description 3
• 206010052779 Transplant rejections Diseases 0.000 claims description 3
• 230000002159 abnormal effect Effects 0.000 claims description 3
• 208000011775 arteriosclerosis disease Diseases 0.000 claims description 3
• 208000006673 asthma Diseases 0.000 claims description 3
• 201000011510 cancer Diseases 0.000 claims description 3
• 229910052799 carbon Inorganic materials 0.000 claims description 3
• 206010008118 cerebral infarction Diseases 0.000 claims description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
• 201000006417 multiple sclerosis Diseases 0.000 claims description 3
• 208000010125 myocardial infarction Diseases 0.000 claims description 3
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
• 229920006395 saturated elastomer Polymers 0.000 claims description 3
• 208000020431 spinal cord injury Diseases 0.000 claims description 3
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 3
• FIOQJQAZLSDRKC-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(3-imidazol-1-ylpropylamino)pyrimidin-4-yl]acetonitrile 2-(1,3-benzothiazol-2-yl)-2-(2-pyrrolidin-1-ylpyrimidin-4-yl)acetonitrile Chemical compound S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)N2CCCC2.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)NCCCN1C=NC=C1 FIOQJQAZLSDRKC-UHFFFAOYSA-N 0.000 claims description 2
• LVNXDCHGOBMXPF-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(4-methylpiperazin-1-yl)pyrimidin-4-yl]acetonitrile 2-(1,3-benzothiazol-2-yl)-2-(2-morpholin-4-ylpyrimidin-4-yl)acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1N1CCOCC1.C1CN(C)CCN1C1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 LVNXDCHGOBMXPF-UHFFFAOYSA-N 0.000 claims description 2
• ADWOTXPHEKVNML-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(4-pyrazin-2-ylpiperazin-1-yl)pyrimidin-4-yl]acetonitrile 2-(1,3-benzothiazol-2-yl)-2-[2-(4-pyrimidin-2-ylpiperazin-1-yl)pyrimidin-4-yl]acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1N(CC1)CCN1C1=CN=CC=N1.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1N(CC1)CCN1C1=NC=CC=N1 ADWOTXPHEKVNML-UHFFFAOYSA-N 0.000 claims description 2
• ALFIAYHEMBNSLM-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(methylamino)pyrimidin-4-yl]acetonitrile 2-(1,3-benzothiazol-2-yl)-2-[2-[4-(2-morpholin-4-ylethyl)piperazin-1-yl]pyrimidin-4-yl]acetonitrile Chemical compound CNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1N(CC1)CCN1CCN1CCOCC1 ALFIAYHEMBNSLM-UHFFFAOYSA-N 0.000 claims description 2
• BDNCPOOPCBONJH-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(pyridin-2-ylmethoxy)pyrimidin-4-yl]acetonitrile 2-(1,3-benzothiazol-2-yl)-2-[2-(pyridin-4-ylmethoxy)pyrimidin-4-yl]acetonitrile Chemical compound N#CC(c1nc2ccccc2s1)c1ccnc(OCc2ccncc2)n1.N#CC(c1nc2ccccc2s1)c1ccnc(OCc2ccccn2)n1 BDNCPOOPCBONJH-UHFFFAOYSA-N 0.000 claims description 2
• FLPWZPQPYWSABF-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[(2-hydroxy-2-phenylethyl)amino]pyrimidin-4-yl]acetonitrile Chemical compound N=1C=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=NC=1NCC(O)C1=CC=CC=C1 FLPWZPQPYWSABF-UHFFFAOYSA-N 0.000 claims description 2
• LFATXMVRHOXIPK-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[(3-phenylphenyl)methoxy]pyrimidin-4-yl]acetonitrile 2-(1,3-benzothiazol-2-yl)-2-[2-[(3,4,5-trimethoxyphenyl)methoxy]pyrimidin-4-yl]acetonitrile Chemical compound COc1cc(COc2nccc(n2)C(C#N)c2nc3ccccc3s2)cc(OC)c1OC.N#CC(c1nc2ccccc2s1)c1ccnc(OCc2cccc(c2)-c2ccccc2)n1 LFATXMVRHOXIPK-UHFFFAOYSA-N 0.000 claims description 2
• VJWNKFBXQSTDQJ-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(3-fluorophenyl)ethylamino]pyrimidin-4-yl]acetonitrile 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(4-phenoxyphenyl)ethylamino]pyrimidin-4-yl]acetonitrile Chemical compound FC1=CC=CC(CCNC=2N=C(C=CN=2)C(C#N)C=2SC3=CC=CC=C3N=2)=C1.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1NCCC(C=C1)=CC=C1OC1=CC=CC=C1 VJWNKFBXQSTDQJ-UHFFFAOYSA-N 0.000 claims description 2
• KIXWDXCFQXGWDX-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(4-bromophenyl)ethylamino]pyrimidin-4-yl]acetonitrile 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(2-phenoxyphenyl)ethylamino]pyrimidin-4-yl]acetonitrile Chemical compound C1=CC(Br)=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1NCCC1=CC=CC=C1OC1=CC=CC=C1 KIXWDXCFQXGWDX-UHFFFAOYSA-N 0.000 claims description 2
• VIVXQUJHDKZCRT-UHFFFAOYSA-N C(C)(=O)N1CCN(CC1)C1=CC=C(OC2=NC=CC(=N2)C(C#N)C=2SC3=C(N2)C=CC=C3)C=C1.S1C(=NC3=C1C=CC=C3)C(C#N)C3=NC(=NC=C3)OC3=CC=C(C=C3)OCCCC Chemical compound C(C)(=O)N1CCN(CC1)C1=CC=C(OC2=NC=CC(=N2)C(C#N)C=2SC3=C(N2)C=CC=C3)C=C1.S1C(=NC3=C1C=CC=C3)C(C#N)C3=NC(=NC=C3)OC3=CC=C(C=C3)OCCCC VIVXQUJHDKZCRT-UHFFFAOYSA-N 0.000 claims description 2
• GFAVIXXZMZDZBK-UHFFFAOYSA-N C1=CC(C)=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1.C1=CC(OC)=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 Chemical compound C1=CC(C)=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1.C1=CC(OC)=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 GFAVIXXZMZDZBK-UHFFFAOYSA-N 0.000 claims description 2
• COCZATAMLYJLIC-UHFFFAOYSA-N C1=CC(F)=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1NCCC(C=C1)=CC=C1C1=CC=CC=C1 Chemical compound C1=CC(F)=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1NCCC(C=C1)=CC=C1C1=CC=CC=C1 COCZATAMLYJLIC-UHFFFAOYSA-N 0.000 claims description 2
• NUEUFKBFSKGNBY-UHFFFAOYSA-N C1=CC(OC)=CC=C1OC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1OCC(C=C1)=CC=C1CN1CCCCC1 Chemical compound C1=CC(OC)=CC=C1OC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1OCC(C=C1)=CC=C1CN1CCCCC1 NUEUFKBFSKGNBY-UHFFFAOYSA-N 0.000 claims description 2
• QAMVYUJEZYVQDF-UHFFFAOYSA-N C1CC(O)CCN1C1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1N(CC1)CCC1OCC1=CC=CC=C1 Chemical compound C1CC(O)CCN1C1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1N(CC1)CCC1OCC1=CC=CC=C1 QAMVYUJEZYVQDF-UHFFFAOYSA-N 0.000 claims description 2
• XLCJLXSANAHXFJ-UHFFFAOYSA-N CCCNc1nccc(n1)C(C#N)c1nc2ccccc2s1.OCCNc1nccc(n1)C(C#N)c1nc2ccccc2s1 Chemical compound CCCNc1nccc(n1)C(C#N)c1nc2ccccc2s1.OCCNc1nccc(n1)C(C#N)c1nc2ccccc2s1 XLCJLXSANAHXFJ-UHFFFAOYSA-N 0.000 claims description 2
• DKCSTXPEJKBPCI-UHFFFAOYSA-N CN(C)CCCNc1nccc(n1)C(C#N)c1nc2ccccc2s1.N#CC(c1nc2ccccc2s1)c1ccnc(NCCN2CCCCC2)n1 Chemical compound CN(C)CCCNc1nccc(n1)C(C#N)c1nc2ccccc2s1.N#CC(c1nc2ccccc2s1)c1ccnc(NCCN2CCCCC2)n1 DKCSTXPEJKBPCI-UHFFFAOYSA-N 0.000 claims description 2
• QAQYGSWKVVMQET-UHFFFAOYSA-N CNCCCN(C)C1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1.C1CN(C)CCN1CCCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 Chemical compound CNCCCN(C)C1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1.C1CN(C)CCN1CCCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 QAQYGSWKVVMQET-UHFFFAOYSA-N 0.000 claims description 2
• NUIWWNMCNIRYRJ-UHFFFAOYSA-N N#CC(c1nc2ccccc2s1)c1ccnc(OCc2cccnc2)n1.COc1ccc(CCOc2nccc(n2)C(C#N)c2nc3ccccc3s2)cc1 Chemical compound N#CC(c1nc2ccccc2s1)c1ccnc(OCc2cccnc2)n1.COc1ccc(CCOc2nccc(n2)C(C#N)c2nc3ccccc3s2)cc1 NUIWWNMCNIRYRJ-UHFFFAOYSA-N 0.000 claims description 2
• QEYWBYAROQVMRA-UHFFFAOYSA-N N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1N1CCNCC1.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1N(CC1)CCC1CC1=CC=CC=C1 Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1N1CCNCC1.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1N(CC1)CCC1CC1=CC=CC=C1 QEYWBYAROQVMRA-UHFFFAOYSA-N 0.000 claims description 2
• VBZBPZDLHCCQDY-UHFFFAOYSA-N NCCNC1=NC=CC(=N1)C(C#N)C=1SC2=C(N1)C=CC=C2.NCCCNC2=NC=CC(=N2)C(C#N)C=2SC1=C(N2)C=CC=C1.C(C)(=O)O Chemical compound NCCNC1=NC=CC(=N1)C(C#N)C=1SC2=C(N1)C=CC=C2.NCCCNC2=NC=CC(=N2)C(C#N)C=2SC1=C(N2)C=CC=C1.C(C)(=O)O VBZBPZDLHCCQDY-UHFFFAOYSA-N 0.000 claims description 2
• 208000018737 Parkinson disease Diseases 0.000 claims description 2
• 206010036790 Productive cough Diseases 0.000 claims description 2
• GLJZSFUKCCNFNX-UHFFFAOYSA-N S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC(=C2)C)Cl.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC(=C1)OC)OC.S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)Cl Chemical compound S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC(=C2)C)Cl.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC(=C1)OC)OC.S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)Cl GLJZSFUKCCNFNX-UHFFFAOYSA-N 0.000 claims description 2
• ALGQNHWKJOQEDK-UHFFFAOYSA-N S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)N2CCC(CC2)N2N=NC1=C2C=CC=C1.S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)NCC2=NC=CC=C2 Chemical compound S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)N2CCC(CC2)N2N=NC1=C2C=CC=C1.S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)NCC2=NC=CC=C2 ALGQNHWKJOQEDK-UHFFFAOYSA-N 0.000 claims description 2
• CBYCUTDMIRADNB-UHFFFAOYSA-N S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)NCCC2=CC(=C(C=C2)Cl)Cl.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)NCCC1=CC(=CC=C1)Cl Chemical compound S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)NCCC2=CC(=C(C=C2)Cl)Cl.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)NCCC1=CC(=CC=C1)Cl CBYCUTDMIRADNB-UHFFFAOYSA-N 0.000 claims description 2
• GMNDQYOZWIUUGV-UHFFFAOYSA-N S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)NCCC2=CC(=CC=C2)C(F)(F)F.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)NCCC1=C(C=CC=C1)F Chemical compound S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)NCCC2=CC(=CC=C2)C(F)(F)F.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)NCCC1=C(C=CC=C1)F GMNDQYOZWIUUGV-UHFFFAOYSA-N 0.000 claims description 2
• SPZAKVBORFQSRE-UHFFFAOYSA-N S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)NCCC2=CC(=CC=C2)OC.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)NCCC1=CC(=C(C=C1)OC)OC Chemical compound S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)NCCC2=CC(=CC=C2)OC.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)NCCC1=CC(=C(C=C1)OC)OC SPZAKVBORFQSRE-UHFFFAOYSA-N 0.000 claims description 2
• SNLHCKBSXRSREX-FOSJCMOUSA-N S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)NCCC2=CN=CN2.ClC2=NC=CC(=N2)\C(\C#N)=C\2/SC1=C(N2C)C=CC=C1 Chemical compound S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)NCCC2=CN=CN2.ClC2=NC=CC(=N2)\C(\C#N)=C\2/SC1=C(N2C)C=CC=C1 SNLHCKBSXRSREX-FOSJCMOUSA-N 0.000 claims description 2
• PIESQVPCTMBRKS-UHFFFAOYSA-N S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)NCCC2=NC=CC=C2.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)NCCC1=CC=CC=C1 Chemical compound S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)NCCC2=NC=CC=C2.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)NCCC1=CC=CC=C1 PIESQVPCTMBRKS-UHFFFAOYSA-N 0.000 claims description 2
• CCGSAYSSTDHWBQ-UHFFFAOYSA-N S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)NCCN(C)C.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)NN Chemical compound S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)NCCN(C)C.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)NN CCGSAYSSTDHWBQ-UHFFFAOYSA-N 0.000 claims description 2
• DMHPWQRCKWJXCW-UHFFFAOYSA-N S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)NCCOC.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)N(C)C Chemical compound S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)NCCOC.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)N(C)C DMHPWQRCKWJXCW-UHFFFAOYSA-N 0.000 claims description 2
• WONUQELSJSFHBV-UHFFFAOYSA-N S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)OCC2=CC(=CC=C2)CN(C)C.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)OCC1=CC(=C(C=C1)Cl)Cl Chemical compound S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)OCC2=CC(=CC=C2)CN(C)C.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)OCC1=CC(=C(C=C1)Cl)Cl WONUQELSJSFHBV-UHFFFAOYSA-N 0.000 claims description 2
• KGMMRTHVRBXJAL-UHFFFAOYSA-N S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)OCC2=CC=C(C=C2)OC.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)OCCCC1=NC=CC=C1 Chemical compound S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)OCC2=CC=C(C=C2)OC.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)OCCCC1=NC=CC=C1 KGMMRTHVRBXJAL-UHFFFAOYSA-N 0.000 claims description 2
• YFLFNWBSQCEHLM-UHFFFAOYSA-N S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)SC.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)Cl Chemical compound S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)SC.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)Cl YFLFNWBSQCEHLM-UHFFFAOYSA-N 0.000 claims description 2
• YFKPRHGYWCCZBP-UHFFFAOYSA-N S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC=NC(=C2[N+](=O)[O-])Cl.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)SC Chemical compound S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC=NC(=C2[N+](=O)[O-])Cl.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)SC YFKPRHGYWCCZBP-UHFFFAOYSA-N 0.000 claims description 2
• CYOBFUFNXDDCKY-UHFFFAOYSA-N S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC=NC=C2.COC2=CC=C(OC1=NC=CC(=N1)C(C#N)C=1SC3=C(N1)C=C(C=C3)C(F)(F)F)C=C2 Chemical compound S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC=NC=C2.COC2=CC=C(OC1=NC=CC(=N1)C(C#N)C=1SC3=C(N1)C=C(C=C3)C(F)(F)F)C=C2 CYOBFUFNXDDCKY-UHFFFAOYSA-N 0.000 claims description 2
• UQDCBBZWNXBOAH-UHFFFAOYSA-N acetonitrile 2-(1,3-benzothiazol-2-yl)-2-[2-[3-(2-oxopyrrolidin-1-yl)propylamino]pyrimidin-4-yl]acetonitrile Chemical compound CC#N.O=C1CCCN1CCCNc1nccc(n1)C(C#N)c1nc2ccccc2s1 UQDCBBZWNXBOAH-UHFFFAOYSA-N 0.000 claims description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 2
• 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
• GWVDAJHAZOYPFH-UHFFFAOYSA-N n-[2-[[4-[1,3-benzothiazol-2-yl(cyano)methyl]pyrimidin-2-yl]amino]ethyl]-4-chlorobenzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 GWVDAJHAZOYPFH-UHFFFAOYSA-N 0.000 claims description 2
• 208000024794 sputum Diseases 0.000 claims description 2
• 210000003802 sputum Anatomy 0.000 claims description 2
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 10
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 7
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 2
• 125000003277 amino group Chemical group 0.000 claims 2
• JMXRTPDXTLQHQQ-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(3-morpholin-4-ylpropylamino)pyrimidin-4-yl]acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1NCCCN1CCOCC1 JMXRTPDXTLQHQQ-UHFFFAOYSA-N 0.000 claims 1
• RCYPVQCPYKNSTG-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(3-pyridinyl)ethylamino]-4-pyrimidinyl]acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1NCCC1=CC=CN=C1 RCYPVQCPYKNSTG-UHFFFAOYSA-N 0.000 claims 1
• QQHCVICNDMKUPJ-UHFFFAOYSA-N 2-[2-(2-pyridin-3-ylethylamino)pyrimidin-4-yl]-2-[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]acetonitrile Chemical compound N=1C2=CC(C(F)(F)F)=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1NCCC1=CC=CN=C1 QQHCVICNDMKUPJ-UHFFFAOYSA-N 0.000 claims 1
• 206010006187 Breast cancer Diseases 0.000 claims 1
• 208000026310 Breast neoplasm Diseases 0.000 claims 1
• 206010009944 Colon cancer Diseases 0.000 claims 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
• 208000025966 Neurological disease Diseases 0.000 claims 1
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
• 230000000996 additive effect Effects 0.000 claims 1
• HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 claims 1
• 125000005843 halogen group Chemical group 0.000 claims 1
• 125000005842 heteroatom Chemical group 0.000 claims 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
• 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 claims 1
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
• 201000002528 pancreatic cancer Diseases 0.000 claims 1
• 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 204
• 238000004128 high performance liquid chromatography Methods 0.000 description 105
• 238000001819 mass spectrum Methods 0.000 description 105
• 238000005160 1H NMR spectroscopy Methods 0.000 description 104
• 150000001875 compounds Chemical class 0.000 description 98
• 210000004027 cell Anatomy 0.000 description 47
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 29
• 239000000243 solution Substances 0.000 description 27
• 239000000203 mixture Substances 0.000 description 24
• 101000950669 Homo sapiens Mitogen-activated protein kinase 9 Proteins 0.000 description 21
• 102100037809 Mitogen-activated protein kinase 9 Human genes 0.000 description 21
• 230000037361 pathway Effects 0.000 description 21
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
• 239000002609 medium Substances 0.000 description 17
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
• 239000000725 suspension Substances 0.000 description 16
• 101000628949 Homo sapiens Mitogen-activated protein kinase 10 Proteins 0.000 description 15
• 102100026931 Mitogen-activated protein kinase 10 Human genes 0.000 description 15
• 239000000843 powder Substances 0.000 description 15
• 239000007858 starting material Substances 0.000 description 15
• 239000012298 atmosphere Substances 0.000 description 12
• 238000002844 melting Methods 0.000 description 12
• 230000008018 melting Effects 0.000 description 12
• 238000012360 testing method Methods 0.000 description 12
• 230000002401 inhibitory effect Effects 0.000 description 11
• 108090000623 proteins and genes Proteins 0.000 description 11
• 102100023482 Mitogen-activated protein kinase 14 Human genes 0.000 description 10
• 102000004169 proteins and genes Human genes 0.000 description 10
• 239000007787 solid Substances 0.000 description 10
• 238000011282 treatment Methods 0.000 description 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
• 102100023132 Transcription factor Jun Human genes 0.000 description 9
• 229910052757 nitrogen Inorganic materials 0.000 description 9
• 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 9
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
• 108010002350 Interleukin-2 Proteins 0.000 description 8
• 102000000588 Interleukin-2 Human genes 0.000 description 8
• 230000006907 apoptotic process Effects 0.000 description 8
• 239000003153 chemical reaction reagent Substances 0.000 description 8
• 210000002569 neuron Anatomy 0.000 description 8
• 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 7
• 108010068304 MAP Kinase Kinase 4 Proteins 0.000 description 7
• 229940125904 compound 1 Drugs 0.000 description 7
• 238000009472 formulation Methods 0.000 description 7
• 239000002244 precipitate Substances 0.000 description 7
• 230000008569 process Effects 0.000 description 7
• 108090000765 processed proteins & peptides Proteins 0.000 description 7
• 102000043136 MAP kinase family Human genes 0.000 description 6
• 108091054455 MAP kinase family Proteins 0.000 description 6
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• 238000004458 analytical method Methods 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• 239000002775 capsule Substances 0.000 description 6
• 239000006285 cell suspension Substances 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 6
• 239000012636 effector Substances 0.000 description 6
• 239000002158 endotoxin Substances 0.000 description 6
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
• 239000002953 phosphate buffered saline Substances 0.000 description 6
• 102000004196 processed proteins & peptides Human genes 0.000 description 6
• 239000002904 solvent Substances 0.000 description 6
• 238000003756 stirring Methods 0.000 description 6
• VZMUTBNJGOPPJS-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-(2-chloro-6-methylpyrimidin-4-yl)acetonitrile Chemical compound ClC1=NC(C)=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 VZMUTBNJGOPPJS-UHFFFAOYSA-N 0.000 description 5
• AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 5
• 102000004127 Cytokines Human genes 0.000 description 5
• 108090000695 Cytokines Proteins 0.000 description 5
• 238000002965 ELISA Methods 0.000 description 5
• 241000699670 Mus sp. Species 0.000 description 5
• 108010025020 Nerve Growth Factor Proteins 0.000 description 5
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
• 125000003342 alkenyl group Chemical group 0.000 description 5
• 210000004556 brain Anatomy 0.000 description 5
• 230000030833 cell death Effects 0.000 description 5
• 230000008859 change Effects 0.000 description 5
• 238000007796 conventional method Methods 0.000 description 5
• 208000035475 disorder Diseases 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 210000000653 nervous system Anatomy 0.000 description 5
• 239000000047 product Substances 0.000 description 5
• 239000011734 sodium Substances 0.000 description 5
• 210000002222 superior cervical ganglion Anatomy 0.000 description 5
• 239000006228 supernatant Substances 0.000 description 5
• TYDPDWCLIXVIFJ-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(4-pyrazin-2-ylpiperazin-1-yl)pyrimidin-4-yl]acetonitrile 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1N(CC1)CCN1C1=CN=CC=N1 TYDPDWCLIXVIFJ-UHFFFAOYSA-N 0.000 description 4
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
• 101000876610 Dictyostelium discoideum Extracellular signal-regulated kinase 2 Proteins 0.000 description 4
• 102100023274 Dual specificity mitogen-activated protein kinase kinase 4 Human genes 0.000 description 4
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 4
• 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 4
• 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 4
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 4
• 101001052493 Homo sapiens Mitogen-activated protein kinase 1 Proteins 0.000 description 4
• 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 4
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
• 210000001744 T-lymphocyte Anatomy 0.000 description 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• 125000004432 carbon atom Chemical group C* 0.000 description 4
• 239000003795 chemical substances by application Substances 0.000 description 4
• 238000001514 detection method Methods 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• 238000000338 in vitro Methods 0.000 description 4
• 238000001727 in vivo Methods 0.000 description 4
• 239000000314 lubricant Substances 0.000 description 4
• 230000007935 neutral effect Effects 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
• ADUDVXJWLLKLOF-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-(2,6-dimethoxypyrimidin-4-yl)acetonitrile Chemical compound COC1=NC(OC)=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 ADUDVXJWLLKLOF-UHFFFAOYSA-N 0.000 description 3
• QVMKLKBODZHJDK-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-(2-chloropyrimidin-4-yl)acetonitrile Chemical compound ClC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 QVMKLKBODZHJDK-UHFFFAOYSA-N 0.000 description 3
• HZYXRWDUVNONMO-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-(2-methylsulfanylpyrimidin-4-yl)acetonitrile Chemical compound CSC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 HZYXRWDUVNONMO-UHFFFAOYSA-N 0.000 description 3
• QSUZXIBKFJPBQR-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-(2-oxo-1h-pyrimidin-6-yl)acetonitrile Chemical compound OC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 QSUZXIBKFJPBQR-UHFFFAOYSA-N 0.000 description 3
• LGPQIPCDUAXDKJ-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-(2-phenylquinazolin-4-yl)acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(C1=CC=CC=C1N=1)=NC=1C1=CC=CC=C1 LGPQIPCDUAXDKJ-UHFFFAOYSA-N 0.000 description 3
• XGRXYXAJEJDAKE-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-(6-chloro-5-nitropyrimidin-4-yl)acetonitrile Chemical compound [O-][N+](=O)C1=C(Cl)N=CN=C1C(C#N)C1=NC2=CC=CC=C2S1 XGRXYXAJEJDAKE-UHFFFAOYSA-N 0.000 description 3
• GDYBTWVWHZIMOE-UHFFFAOYSA-N 2-(2-chloropyrimidin-4-yl)-2-[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]acetonitrile Chemical compound N=1C2=CC(C(F)(F)F)=CC=C2SC=1C(C#N)C1=CC=NC(Cl)=N1 GDYBTWVWHZIMOE-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• 0 Cc1nc(Cl)nc(*)c1Br Chemical compound Cc1nc(Cl)nc(*)c1Br 0.000 description 3
• 108020004414 DNA Proteins 0.000 description 3
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
• 108010010803 Gelatin Proteins 0.000 description 3
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
• 239000012825 JNK inhibitor Substances 0.000 description 3
• 102000002569 MAP Kinase Kinase 4 Human genes 0.000 description 3
• 241000124008 Mammalia Species 0.000 description 3
• 241000699666 Mus <mouse, genus> Species 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 241000242739 Renilla Species 0.000 description 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
• 230000005856 abnormality Effects 0.000 description 3
• 235000011054 acetic acid Nutrition 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 150000001298 alcohols Chemical class 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 230000001640 apoptogenic effect Effects 0.000 description 3
• 230000001363 autoimmune Effects 0.000 description 3
• 239000011324 bead Substances 0.000 description 3
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
• 239000011230 binding agent Substances 0.000 description 3
• 238000004113 cell culture Methods 0.000 description 3
• 239000013553 cell monolayer Substances 0.000 description 3
• 238000012258 culturing Methods 0.000 description 3
• 230000034994 death Effects 0.000 description 3
• 239000002552 dosage form Substances 0.000 description 3
• 229920000159 gelatin Polymers 0.000 description 3
• 239000008273 gelatin Substances 0.000 description 3
• 235000019322 gelatine Nutrition 0.000 description 3
• 235000011852 gelatine desserts Nutrition 0.000 description 3
• 210000001320 hippocampus Anatomy 0.000 description 3
• 230000036039 immunity Effects 0.000 description 3
• 239000003112 inhibitor Substances 0.000 description 3
• 239000007972 injectable composition Substances 0.000 description 3
• 208000028867 ischemia Diseases 0.000 description 3
• 235000019359 magnesium stearate Nutrition 0.000 description 3
• 230000001404 mediated effect Effects 0.000 description 3
• 239000012528 membrane Substances 0.000 description 3
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• 210000005036 nerve Anatomy 0.000 description 3
• 230000004770 neurodegeneration Effects 0.000 description 3
• 208000015122 neurodegenerative disease Diseases 0.000 description 3
• 239000003921 oil Substances 0.000 description 3
• 239000011780 sodium chloride Substances 0.000 description 3
• 229910000104 sodium hydride Inorganic materials 0.000 description 3
• 230000035882 stress Effects 0.000 description 3
• 239000000758 substrate Substances 0.000 description 3
• 239000012730 sustained-release form Substances 0.000 description 3
• 230000002889 sympathetic effect Effects 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• 238000010998 test method Methods 0.000 description 3
• 238000001890 transfection Methods 0.000 description 3
• MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
• BTTNYQZNBZNDOR-UHFFFAOYSA-N 2,4-dichloropyrimidine Chemical compound ClC1=CC=NC(Cl)=N1 BTTNYQZNBZNDOR-UHFFFAOYSA-N 0.000 description 2
• YPLNLOJZEWIBMR-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-(2-phenylmethoxypyrimidin-4-yl)acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1OCC1=CC=CC=C1 YPLNLOJZEWIBMR-UHFFFAOYSA-N 0.000 description 2
• XBEFSRNAEJKXGZ-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-(2-pyrrolidin-1-ylpyrimidin-4-yl)acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1N1CCCC1 XBEFSRNAEJKXGZ-UHFFFAOYSA-N 0.000 description 2
• WPNCEEINDOKBFX-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(2-hydroxyethylamino)pyrimidin-4-yl]acetonitrile Chemical compound OCCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 WPNCEEINDOKBFX-UHFFFAOYSA-N 0.000 description 2
• XWLZOTIIMHICFH-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(2-methoxyethylamino)pyrimidin-4-yl]acetonitrile Chemical compound COCCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 XWLZOTIIMHICFH-UHFFFAOYSA-N 0.000 description 2
• SCKGBURIWVFYFI-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(2-phenylethylamino)pyrimidin-4-yl]acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1NCCC1=CC=CC=C1 SCKGBURIWVFYFI-UHFFFAOYSA-N 0.000 description 2
• VGBABLLAZLCFRS-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(2H-tetrazol-5-ylmethylamino)pyrimidin-4-yl]acetonitrile 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1NCC1=NN=NN1 VGBABLLAZLCFRS-UHFFFAOYSA-N 0.000 description 2
• YTAFCWVQZLIYBY-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(3-imidazol-1-ylpropylamino)pyrimidin-4-yl]acetonitrile 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1NCCCN1C=CN=C1 YTAFCWVQZLIYBY-UHFFFAOYSA-N 0.000 description 2
• TXRVBRCNEHRVKC-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(4-benzylpiperidin-1-yl)pyrimidin-4-yl]acetonitrile 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1N(CC1)CCC1CC1=CC=CC=C1 TXRVBRCNEHRVKC-UHFFFAOYSA-N 0.000 description 2
• ICVMIWYOLXKRIJ-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(4-butoxyphenoxy)pyrimidin-4-yl]acetonitrile Chemical compound C1=CC(OCCCC)=CC=C1OC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 ICVMIWYOLXKRIJ-UHFFFAOYSA-N 0.000 description 2
• DOJMTDCTCJKZNL-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(4-methoxyphenoxy)pyrimidin-4-yl]acetonitrile Chemical compound C1=CC(OC)=CC=C1OC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 DOJMTDCTCJKZNL-UHFFFAOYSA-N 0.000 description 2
• JBOHGFWMTSRPMY-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(benzylamino)pyrimidin-4-yl]acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1NCC1=CC=CC=C1 JBOHGFWMTSRPMY-UHFFFAOYSA-N 0.000 description 2
• NNNOORSBALRCHT-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(propylamino)pyrimidin-4-yl]acetonitrile Chemical compound CCCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 NNNOORSBALRCHT-UHFFFAOYSA-N 0.000 description 2
• UKIADQJYGDXNOV-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(pyridin-3-ylmethoxy)pyrimidin-4-yl]acetonitrile 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1OCC1=CC=CN=C1 UKIADQJYGDXNOV-UHFFFAOYSA-N 0.000 description 2
• FMJSALIQRYKGSC-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(pyridin-4-ylmethoxy)pyrimidin-4-yl]acetonitrile 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1OCC1=CC=NC=C1 FMJSALIQRYKGSC-UHFFFAOYSA-N 0.000 description 2
• JVXCVACFVKUPMQ-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[(2-hydroxy-2-phenylethyl)amino]pyrimidin-4-yl]acetonitrile 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N=1C=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=NC=1NCC(O)C1=CC=CC=C1 JVXCVACFVKUPMQ-UHFFFAOYSA-N 0.000 description 2
• SZLPBHGDRGQGRW-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[(3,4,5-trimethoxyphenyl)methoxy]pyrimidin-4-yl]acetonitrile Chemical compound COC1=C(OC)C(OC)=CC(COC=2N=C(C=CN=2)C(C#N)C=2SC3=CC=CC=C3N=2)=C1 SZLPBHGDRGQGRW-UHFFFAOYSA-N 0.000 description 2
• DNTIGMKOHTVCHE-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[(3,4-dichlorophenyl)methoxy]pyrimidin-4-yl]acetonitrile Chemical compound C1=C(Cl)C(Cl)=CC=C1COC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 DNTIGMKOHTVCHE-UHFFFAOYSA-N 0.000 description 2
• RBJLZPCTOBPFRV-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[(3-phenylphenyl)methoxy]pyrimidin-4-yl]acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1OCC(C=1)=CC=CC=1C1=CC=CC=C1 RBJLZPCTOBPFRV-UHFFFAOYSA-N 0.000 description 2
• KBCDRFGLNAFYKS-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[(4-methoxyphenyl)methoxy]pyrimidin-4-yl]acetonitrile Chemical compound C1=CC(OC)=CC=C1COC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 KBCDRFGLNAFYKS-UHFFFAOYSA-N 0.000 description 2
• BZPBALIWTDEWOB-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[(4-pyridin-2-ylphenyl)methoxy]pyrimidin-4-yl]acetonitrile 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1OCC(C=C1)=CC=C1C1=CC=CC=N1 BZPBALIWTDEWOB-UHFFFAOYSA-N 0.000 description 2
• DEKSZEZKKDUYNO-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[(4-pyridin-3-ylphenyl)methoxy]pyrimidin-4-yl]acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1OCC(C=C1)=CC=C1C1=CC=CN=C1 DEKSZEZKKDUYNO-UHFFFAOYSA-N 0.000 description 2
• AXEBCVIPELYPGM-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(1,2,4-triazol-1-yl)ethylamino]pyrimidin-4-yl]acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1NCCN1C=NC=N1 AXEBCVIPELYPGM-UHFFFAOYSA-N 0.000 description 2
• OVSRYNZJXPTZSB-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(1-methylimidazol-4-yl)ethylamino]pyrimidin-4-yl]acetonitrile Chemical compound CN1C=NC(CCNC=2N=C(C=CN=2)C(C#N)C=2SC3=CC=CC=C3N=2)=C1 OVSRYNZJXPTZSB-UHFFFAOYSA-N 0.000 description 2
• ZXQRSRUXXGBKRC-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(1h-imidazol-5-yl)ethylamino]pyrimidin-4-yl]acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1NCCC1=CNC=N1 ZXQRSRUXXGBKRC-UHFFFAOYSA-N 0.000 description 2
• CZYBPTILBCPFLX-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(1h-indol-3-yl)ethylamino]pyrimidin-4-yl]acetonitrile Chemical compound C1=CC=C2C(CCNC=3N=CC=C(N=3)C(C=3SC4=CC=CC=C4N=3)C#N)=CNC2=C1 CZYBPTILBCPFLX-UHFFFAOYSA-N 0.000 description 2
• BIZJCJPDVVRBDV-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(2-fluorophenyl)ethylamino]pyrimidin-4-yl]acetonitrile Chemical compound FC1=CC=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 BIZJCJPDVVRBDV-UHFFFAOYSA-N 0.000 description 2
• USFPIALROBEEQD-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(2-phenoxyphenyl)ethylamino]pyrimidin-4-yl]acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1NCCC1=CC=CC=C1OC1=CC=CC=C1 USFPIALROBEEQD-UHFFFAOYSA-N 0.000 description 2
• UEIAVWHMLMESNO-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(3,4-dichlorophenyl)ethylamino]pyrimidin-4-yl]acetonitrile 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(Cl)C(Cl)=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 UEIAVWHMLMESNO-UHFFFAOYSA-N 0.000 description 2
• KSTCTALKPRMJBB-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(3,4-dimethoxyphenyl)ethylamino]pyrimidin-4-yl]acetonitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 KSTCTALKPRMJBB-UHFFFAOYSA-N 0.000 description 2
• KCFGJHRVDPDFCP-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(3-methoxyphenyl)ethylamino]pyrimidin-4-yl]acetonitrile Chemical compound COC1=CC=CC(CCNC=2N=C(C=CN=2)C(C#N)C=2SC3=CC=CC=C3N=2)=C1 KCFGJHRVDPDFCP-UHFFFAOYSA-N 0.000 description 2
• JVXMSFVUVMWIBX-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(4-bromophenyl)ethylamino]pyrimidin-4-yl]acetonitrile Chemical compound C1=CC(Br)=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 JVXMSFVUVMWIBX-UHFFFAOYSA-N 0.000 description 2
• WFMLPVJXAXUUNG-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(4-fluorophenyl)ethylamino]pyrimidin-4-yl]acetonitrile Chemical compound C1=CC(F)=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 WFMLPVJXAXUUNG-UHFFFAOYSA-N 0.000 description 2
• BIDRVSQGIUDCOE-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(4-hydroxyphenyl)ethylamino]pyrimidin-4-yl]acetonitrile Chemical compound C1=CC(O)=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 BIDRVSQGIUDCOE-UHFFFAOYSA-N 0.000 description 2
• DWJOMGAJOLCYJP-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(4-methoxyphenyl)ethoxy]pyrimidin-4-yl]acetonitrile Chemical compound C1=CC(OC)=CC=C1CCOC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 DWJOMGAJOLCYJP-UHFFFAOYSA-N 0.000 description 2
• WXGMYJPKKCMTOC-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(4-phenoxyphenyl)ethylamino]pyrimidin-4-yl]acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1NCCC(C=C1)=CC=C1OC1=CC=CC=C1 WXGMYJPKKCMTOC-UHFFFAOYSA-N 0.000 description 2
• XUBUGOICWPOBPA-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(4-phenylphenyl)ethylamino]pyrimidin-4-yl]acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1NCCC(C=C1)=CC=C1C1=CC=CC=C1 XUBUGOICWPOBPA-UHFFFAOYSA-N 0.000 description 2
• XPPXMRFMYJEOQV-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-[3-(trifluoromethyl)phenyl]ethylamino]pyrimidin-4-yl]acetonitrile Chemical compound FC(F)(F)C1=CC=CC(CCNC=2N=C(C=CN=2)C(C#N)C=2SC3=CC=CC=C3N=2)=C1 XPPXMRFMYJEOQV-UHFFFAOYSA-N 0.000 description 2
• LFQHFPFMSFXHGG-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[[3-[(dimethylamino)methyl]phenyl]methoxy]pyrimidin-4-yl]acetonitrile 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CN(C)CC1=CC=CC(COC=2N=C(C=CN=2)C(C#N)C=2SC3=CC=CC=C3N=2)=C1 LFQHFPFMSFXHGG-UHFFFAOYSA-N 0.000 description 2
• ZGCWUWYHVSNRRT-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[[4-(morpholin-4-ylmethyl)phenyl]methoxy]pyrimidin-4-yl]acetonitrile 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1OCC(C=C1)=CC=C1CN1CCOCC1 ZGCWUWYHVSNRRT-UHFFFAOYSA-N 0.000 description 2
• AVUMOZKOAABSTP-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[5-bromo-2-[2-(dimethylamino)ethylamino]pyrimidin-4-yl]acetonitrile Chemical compound CN(C)CCNC1=NC=C(Br)C(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 AVUMOZKOAABSTP-UHFFFAOYSA-N 0.000 description 2
• DHKGFPAGTPKCSZ-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-pyrimidin-4-ylacetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C1=CC=NC=N1 DHKGFPAGTPKCSZ-UHFFFAOYSA-N 0.000 description 2
• XBZOJZPBVXNZAN-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-2-(1,3-benzothiazol-2-yl)acetonitrile Chemical compound NC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 XBZOJZPBVXNZAN-UHFFFAOYSA-N 0.000 description 2
• BYCKAWVPBBQBMJ-UHFFFAOYSA-N 2-[2-(4-methoxyphenoxy)pyrimidin-4-yl]-2-[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]acetonitrile Chemical compound C1=CC(OC)=CC=C1OC1=NC=CC(C(C#N)C=2SC3=CC=C(C=C3N=2)C(F)(F)F)=N1 BYCKAWVPBBQBMJ-UHFFFAOYSA-N 0.000 description 2
• NMZGZFQXIRKEHD-UHFFFAOYSA-N 2-[2-[4-(4-acetylpiperazin-1-yl)phenoxy]pyrimidin-4-yl]-2-(1,3-benzothiazol-2-yl)acetonitrile Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 NMZGZFQXIRKEHD-UHFFFAOYSA-N 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 239000005711 Benzoic acid Substances 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• 101710105206 C-Jun-amino-terminal kinase-interacting protein 1 Proteins 0.000 description 2
• 102100022291 C-Jun-amino-terminal kinase-interacting protein 1 Human genes 0.000 description 2
• CIMRIDPPEONTRF-UHFFFAOYSA-N C1=CC=C2C(=C1)N=C(S2)C(C#N)C3=NC(=NC=C3)NCCC4=CN=CC=C4.C(=O)(C(F)(F)F)O.C(=O)(C(F)(F)F)O Chemical compound C1=CC=C2C(=C1)N=C(S2)C(C#N)C3=NC(=NC=C3)NCCC4=CN=CC=C4.C(=O)(C(F)(F)F)O.C(=O)(C(F)(F)F)O CIMRIDPPEONTRF-UHFFFAOYSA-N 0.000 description 2
• 206010010904 Convulsion Diseases 0.000 description 2
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
• 102100023275 Dual specificity mitogen-activated protein kinase kinase 3 Human genes 0.000 description 2
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
• 229940118135 JNK inhibitor Drugs 0.000 description 2
• 101710166851 JNK-interacting protein 1 Proteins 0.000 description 2
• 108010068355 MAP Kinase Kinase 3 Proteins 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
• YHWFFKOQAAXXMF-UHFFFAOYSA-N OC(=O)C(F)(F)F.C1=CC(C)=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 Chemical compound OC(=O)C(F)(F)F.C1=CC(C)=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 YHWFFKOQAAXXMF-UHFFFAOYSA-N 0.000 description 2
• GXCDPWOMYMAQEL-UHFFFAOYSA-N OC(=O)C(F)(F)F.C1=CC(OC)=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 Chemical compound OC(=O)C(F)(F)F.C1=CC(OC)=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 GXCDPWOMYMAQEL-UHFFFAOYSA-N 0.000 description 2
• PJCFQELNMOYWOJ-UHFFFAOYSA-N OC(=O)C(F)(F)F.C1CC(O)CCN1C1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 Chemical compound OC(=O)C(F)(F)F.C1CC(O)CCN1C1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 PJCFQELNMOYWOJ-UHFFFAOYSA-N 0.000 description 2
• GPCCICBCXGQKOM-UHFFFAOYSA-N OC(=O)C(F)(F)F.ClC1=CC=CC(CCNC=2N=C(C=CN=2)C(C#N)C=2SC3=CC=CC=C3N=2)=C1 Chemical compound OC(=O)C(F)(F)F.ClC1=CC=CC(CCNC=2N=C(C=CN=2)C(C#N)C=2SC3=CC=CC=C3N=2)=C1 GPCCICBCXGQKOM-UHFFFAOYSA-N 0.000 description 2
• BIBFTDGFKQSSHY-UHFFFAOYSA-N OC(=O)C(F)(F)F.FC(F)(F)S(=O)(=O)C1=CC=CC(NC2CCN(CC2)C=2N=C(C=CN=2)C(C#N)C=2SC3=CC=CC=C3N=2)=C1 Chemical compound OC(=O)C(F)(F)F.FC(F)(F)S(=O)(=O)C1=CC=CC(NC2CCN(CC2)C=2N=C(C=CN=2)C(C#N)C=2SC3=CC=CC=C3N=2)=C1 BIBFTDGFKQSSHY-UHFFFAOYSA-N 0.000 description 2
• PPGUPTPUUOUWFH-UHFFFAOYSA-N OC(=O)C(F)(F)F.FC1=CC=CC(CCNC=2N=C(C=CN=2)C(C#N)C=2SC3=CC=CC=C3N=2)=C1 Chemical compound OC(=O)C(F)(F)F.FC1=CC=CC(CCNC=2N=C(C=CN=2)C(C#N)C=2SC3=CC=CC=C3N=2)=C1 PPGUPTPUUOUWFH-UHFFFAOYSA-N 0.000 description 2
• GQDYMQDSTMWJEZ-UHFFFAOYSA-N OC(=O)C(F)(F)F.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1N(CC1)CCC1OCC1=CC=CC=C1 Chemical compound OC(=O)C(F)(F)F.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1N(CC1)CCC1OCC1=CC=CC=C1 GQDYMQDSTMWJEZ-UHFFFAOYSA-N 0.000 description 2
• JPZUREOZZLNSTH-UHFFFAOYSA-N OC(=O)C(F)(F)F.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1N1CCOCC1 Chemical compound OC(=O)C(F)(F)F.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1N1CCOCC1 JPZUREOZZLNSTH-UHFFFAOYSA-N 0.000 description 2
• XMMZJYHPTMXBRN-UHFFFAOYSA-N OC(=O)C(F)(F)F.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1OCC(C=C1)=CC=C1CN1CCCCC1 Chemical compound OC(=O)C(F)(F)F.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1OCC(C=C1)=CC=C1CN1CCCCC1 XMMZJYHPTMXBRN-UHFFFAOYSA-N 0.000 description 2
• HIDSVCLPFSSITB-UHFFFAOYSA-N OC(=O)C(F)(F)F.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1OCC1=CC=CC=N1 Chemical compound OC(=O)C(F)(F)F.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1OCC1=CC=CC=N1 HIDSVCLPFSSITB-UHFFFAOYSA-N 0.000 description 2
• DZCYYQZAJYUYKB-UHFFFAOYSA-N OC(=O)C(F)(F)F.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1OCCCC1=CC=CC=N1 Chemical compound OC(=O)C(F)(F)F.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1OCCCC1=CC=CC=N1 DZCYYQZAJYUYKB-UHFFFAOYSA-N 0.000 description 2
• SGKIRXPOIGMTTN-UHFFFAOYSA-N OC(=O)C(F)(F)F.NNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 Chemical compound OC(=O)C(F)(F)F.NNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 SGKIRXPOIGMTTN-UHFFFAOYSA-N 0.000 description 2
• MOIQCLSFUCYWDF-UHFFFAOYSA-N OC(=O)C(F)(F)F.O=C1CCCN1CCCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 Chemical compound OC(=O)C(F)(F)F.O=C1CCCN1CCCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 MOIQCLSFUCYWDF-UHFFFAOYSA-N 0.000 description 2
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
• 206010057249 Phagocytosis Diseases 0.000 description 2
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 108091008874 T cell receptors Proteins 0.000 description 2
• 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 2
• 210000000447 Th1 cell Anatomy 0.000 description 2
• 210000004241 Th2 cell Anatomy 0.000 description 2
• 229920004890 Triton X-100 Polymers 0.000 description 2
• 239000013504 Triton X-100 Substances 0.000 description 2
• 102000004142 Trypsin Human genes 0.000 description 2
• 108090000631 Trypsin Proteins 0.000 description 2
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
• 238000002835 absorbance Methods 0.000 description 2
• 239000002253 acid Substances 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 239000004480 active ingredient Substances 0.000 description 2
• 239000000783 alginic acid Substances 0.000 description 2
• 235000010443 alginic acid Nutrition 0.000 description 2
• 229920000615 alginic acid Polymers 0.000 description 2
• 229960001126 alginic acid Drugs 0.000 description 2
• 150000004781 alginic acids Chemical class 0.000 description 2
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
• 210000000612 antigen-presenting cell Anatomy 0.000 description 2
• 239000011668 ascorbic acid Substances 0.000 description 2
• 235000010323 ascorbic acid Nutrition 0.000 description 2
• 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical class C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• 239000008280 blood Substances 0.000 description 2
• 210000000481 breast Anatomy 0.000 description 2
• 239000012267 brine Substances 0.000 description 2
• 239000007975 buffered saline Substances 0.000 description 2
• 230000003833 cell viability Effects 0.000 description 2
• 229910052801 chlorine Inorganic materials 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• 230000004069 differentiation Effects 0.000 description 2
• 230000002222 downregulating effect Effects 0.000 description 2
• 238000001035 drying Methods 0.000 description 2
• 239000012039 electrophile Substances 0.000 description 2
• 230000003492 excitotoxic effect Effects 0.000 description 2
• 231100000063 excitotoxicity Toxicity 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 235000019634 flavors Nutrition 0.000 description 2
• 238000013467 fragmentation Methods 0.000 description 2
• 238000006062 fragmentation reaction Methods 0.000 description 2
• 238000007429 general method Methods 0.000 description 2
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
• 229960001340 histamine Drugs 0.000 description 2
• 208000026278 immune system disease Diseases 0.000 description 2
• 230000001939 inductive effect Effects 0.000 description 2
• 230000002757 inflammatory effect Effects 0.000 description 2
• 230000028709 inflammatory response Effects 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
• PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 2
• PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 2
• QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
• 239000008108 microcrystalline cellulose Substances 0.000 description 2
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
• 229940016286 microcrystalline cellulose Drugs 0.000 description 2
• 125000001624 naphthyl group Chemical group 0.000 description 2
• 239000013642 negative control Substances 0.000 description 2
• 230000016273 neuron death Effects 0.000 description 2
• 230000009223 neuronal apoptosis Effects 0.000 description 2
• 239000012074 organic phase Substances 0.000 description 2
• PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 description 2
• NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 2
• 210000000496 pancreas Anatomy 0.000 description 2
• 208000024691 pancreas disease Diseases 0.000 description 2
• WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
• 230000008782 phagocytosis Effects 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• 230000026731 phosphorylation Effects 0.000 description 2
• 238000006366 phosphorylation reaction Methods 0.000 description 2
• 229920001184 polypeptide Polymers 0.000 description 2
• 229920000136 polysorbate Polymers 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• 229910000027 potassium carbonate Inorganic materials 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 230000019491 signal transduction Effects 0.000 description 2
• 239000002356 single layer Substances 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 239000012089 stop solution Substances 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 238000013268 sustained release Methods 0.000 description 2
• WGTYBPLFGIVFAS-UHFFFAOYSA-M tetramethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C WGTYBPLFGIVFAS-UHFFFAOYSA-M 0.000 description 2
• 210000001519 tissue Anatomy 0.000 description 2
• 239000012588 trypsin Substances 0.000 description 2
• 239000011534 wash buffer Substances 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• GRRNUXAQVGOGFE-XKIAHZFYSA-N (2s,3'r,3as,4s,4's,5'r,6r,6'r,7s,7as)-4-[(1r,2s,3r,5s,6r)-3-amino-2,6-dihydroxy-5-(methylamino)cyclohexyl]oxy-6'-[(1r)-1-amino-2-hydroxyethyl]-6-(hydroxymethyl)spiro[4,6,7,7a-tetrahydro-3ah-[1,3]dioxolo[4,5-c]pyran-2,2'-oxane]-3',4',5',7-tetrol Chemical compound O[C@@H]1[C@@H](NC)C[C@@H](N)[C@H](O)[C@H]1O[C@H]1[C@H]2O[C@]3([C@@H]([C@@H](O)[C@@H](O)[C@@H]([C@H](N)CO)O3)O)O[C@H]2[C@@H](O)[C@@H](CO)O1 GRRNUXAQVGOGFE-XKIAHZFYSA-N 0.000 description 1
• YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
• 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
• 125000004529 1,2,3-triazinyl group Chemical group N1=NN=C(C=C1)* 0.000 description 1
• 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
• 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 1
• 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
• TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
• PYHXGXCGESYPCW-UHFFFAOYSA-M 2,2-diphenylacetate Chemical compound C=1C=CC=CC=1C(C(=O)[O-])C1=CC=CC=C1 PYHXGXCGESYPCW-UHFFFAOYSA-M 0.000 description 1
• AHDSRXYHVZECER-UHFFFAOYSA-N 2,4,6-tris[(dimethylamino)methyl]phenol Chemical compound CN(C)CC1=CC(CN(C)C)=C(O)C(CN(C)C)=C1 AHDSRXYHVZECER-UHFFFAOYSA-N 0.000 description 1
• ODCLSTIOISSVGF-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(methylamino)pyrimidin-4-yl]acetonitrile Chemical compound CNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 ODCLSTIOISSVGF-UHFFFAOYSA-N 0.000 description 1
• JPKDYRJUCJAWST-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(pyridin-3-ylmethylamino)pyrimidin-4-yl]acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1NCC1=CC=CN=C1 JPKDYRJUCJAWST-UHFFFAOYSA-N 0.000 description 1
• QHPXOPWCQBDGPX-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(pyridin-4-ylmethylamino)pyrimidin-4-yl]acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1NCC1=CC=NC=C1 QHPXOPWCQBDGPX-UHFFFAOYSA-N 0.000 description 1
• RIMQLZSCJYYTPV-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(3-methylimidazol-4-yl)ethylamino]pyrimidin-4-yl]acetonitrile Chemical compound CN1C=NC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 RIMQLZSCJYYTPV-UHFFFAOYSA-N 0.000 description 1
• NWMOQMBMVRDYLN-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[3-(4-methylpiperazin-1-yl)propylamino]pyrimidin-4-yl]acetonitrile Chemical compound C1CN(C)CCN1CCCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 NWMOQMBMVRDYLN-UHFFFAOYSA-N 0.000 description 1
• GRMMETGASZZNCC-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[3-(dimethylamino)propylamino]pyrimidin-4-yl]acetonitrile Chemical compound CN(C)CCCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 GRMMETGASZZNCC-UHFFFAOYSA-N 0.000 description 1
• QLBGFCHJCWNVIN-UHFFFAOYSA-N 2-(1,3-thiazol-2-yl)acetonitrile Chemical compound N#CCC1=NC=CS1 QLBGFCHJCWNVIN-UHFFFAOYSA-N 0.000 description 1
• PYGYNJXSCBKNBG-UHFFFAOYSA-N 2-[2-[2-(4-aminophenyl)ethylamino]pyrimidin-4-yl]-2-(1,3-benzothiazol-2-yl)acetonitrile Chemical compound C1=CC(N)=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 PYGYNJXSCBKNBG-UHFFFAOYSA-N 0.000 description 1
• KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 1
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
• OKDGRDCXVWSXDC-UHFFFAOYSA-N 2-chloropyridine Chemical compound ClC1=CC=CC=N1 OKDGRDCXVWSXDC-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
• RKIDDEGICSMIJA-UHFFFAOYSA-N 4-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C=C1 RKIDDEGICSMIJA-UHFFFAOYSA-N 0.000 description 1
• KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• 206010002091 Anaesthesia Diseases 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 230000003844 B-cell-activation Effects 0.000 description 1
• YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
• GVJKODHWVQJHSB-UHFFFAOYSA-N C1=CC(O)=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1.C1=CC=C2C(CCNC=3N=CC=C(N=3)C(C=3SC4=CC=CC=C4N=3)C#N)=CNC2=C1 Chemical compound C1=CC(O)=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1.C1=CC=C2C(CCNC=3N=CC=C(N=3)C(C=3SC4=CC=CC=C4N=3)C#N)=CNC2=C1 GVJKODHWVQJHSB-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• IIALSLVGUGOODS-UHFFFAOYSA-N Cc(nc(nc1)Cl)c1Br Chemical compound Cc(nc(nc1)Cl)c1Br IIALSLVGUGOODS-UHFFFAOYSA-N 0.000 description 1
• OLECIUDZMBISNS-UHFFFAOYSA-N Cc(nc(nc1)SC)c1F Chemical compound Cc(nc(nc1)SC)c1F OLECIUDZMBISNS-UHFFFAOYSA-N 0.000 description 1
• MDZCNJHECVPINP-UHFFFAOYSA-N Cc(nc(nc1C)Cl)c1Br Chemical compound Cc(nc(nc1C)Cl)c1Br MDZCNJHECVPINP-UHFFFAOYSA-N 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 108010077544 Chromatin Proteins 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 102000008186 Collagen Human genes 0.000 description 1
• 108010035532 Collagen Proteins 0.000 description 1
• 208000019399 Colonic disease Diseases 0.000 description 1
• 206010010144 Completed suicide Diseases 0.000 description 1
• FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 102100023033 Cyclic AMP-dependent transcription factor ATF-2 Human genes 0.000 description 1
• 230000005778 DNA damage Effects 0.000 description 1
• 231100000277 DNA damage Toxicity 0.000 description 1
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 239000001263 FEMA 3042 Substances 0.000 description 1
• 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
• 241000699694 Gerbillinae Species 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000974934 Homo sapiens Cyclic AMP-dependent transcription factor ATF-2 Proteins 0.000 description 1
• 101000997829 Homo sapiens Glial cell line-derived neurotrophic factor Proteins 0.000 description 1
• 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 1
• 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
• 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 108090000174 Interleukin-10 Proteins 0.000 description 1
• 108090000176 Interleukin-13 Proteins 0.000 description 1
• 108090000978 Interleukin-4 Proteins 0.000 description 1
• 108010002616 Interleukin-5 Proteins 0.000 description 1
• 108090001005 Interleukin-6 Proteins 0.000 description 1
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
• YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 108060001084 Luciferase Proteins 0.000 description 1
• 239000005089 Luciferase Substances 0.000 description 1
• 102000004083 Lymphotoxin-alpha Human genes 0.000 description 1
• 108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
• 102000001291 MAP Kinase Kinase Kinase Human genes 0.000 description 1
• 108060006687 MAP kinase kinase kinase Proteins 0.000 description 1
• 235000011430 Malus pumila Nutrition 0.000 description 1
• 235000015103 Malus silvestris Nutrition 0.000 description 1
• 244000246386 Mentha pulegium Species 0.000 description 1
• 235000016257 Mentha pulegium Nutrition 0.000 description 1
• 235000004357 Mentha x piperita Nutrition 0.000 description 1
• 102000005741 Metalloproteases Human genes 0.000 description 1
• 108010006035 Metalloproteases Proteins 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
• 102000047918 Myelin Basic Human genes 0.000 description 1
• 101710107068 Myelin basic protein Proteins 0.000 description 1
• QHOQZLMMXDYEGA-UHFFFAOYSA-N N#CC(c1nc2ccccc2s1)c1ccnc(OCc2ccccc2)n1.N#CC(c1nc2ccccc2s1)c1ccnc(OCc2ccc(cc2)-c2cccnc2)n1 Chemical compound N#CC(c1nc2ccccc2s1)c1ccnc(OCc2ccccc2)n1.N#CC(c1nc2ccccc2s1)c1ccnc(OCc2ccc(cc2)-c2cccnc2)n1 QHOQZLMMXDYEGA-UHFFFAOYSA-N 0.000 description 1
• XRACIFFMEJNEMK-UHFFFAOYSA-N N-[2-[[4-[1,3-benzothiazol-2-yl(cyano)methyl]pyrimidin-2-yl]amino]ethyl]-4-chlorobenzamide 2-(1,3-benzothiazol-2-yl)-2-(2-methoxypyrimidin-4-yl)acetonitrile Chemical compound COC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1.C1=CC(Cl)=CC=C1C(=O)NCCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 XRACIFFMEJNEMK-UHFFFAOYSA-N 0.000 description 1
• CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
• 238000005481 NMR spectroscopy Methods 0.000 description 1
• LPBDZVNGCNTELM-UHFFFAOYSA-N Nc1ccnc(Cl)n1 Chemical compound Nc1ccnc(Cl)n1 LPBDZVNGCNTELM-UHFFFAOYSA-N 0.000 description 1
• 206010028851 Necrosis Diseases 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 239000006057 Non-nutritive feed additive Substances 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 208000037273 Pathologic Processes Diseases 0.000 description 1
• 229920002230 Pectic acid Polymers 0.000 description 1
• LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 108010020346 Polyglutamic Acid Proteins 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
• 102100027584 Protein c-Fos Human genes 0.000 description 1
• 108010071563 Proto-Oncogene Proteins c-fos Proteins 0.000 description 1
• 239000012980 RPMI-1640 medium Substances 0.000 description 1
• 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
• NFZKPCATJGRVDT-UHFFFAOYSA-N S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)NCC2=CC=CC=C2.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)NCCC1=CN=CN1C Chemical compound S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)NCC2=CC=CC=C2.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)NCCC1=CN=CN1C NFZKPCATJGRVDT-UHFFFAOYSA-N 0.000 description 1
• 229940124639 Selective inhibitor Drugs 0.000 description 1
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 1
• 108010090804 Streptavidin Proteins 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 230000006044 T cell activation Effects 0.000 description 1
• 230000006052 T cell proliferation Effects 0.000 description 1
• 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
• 230000029662 T-helper 1 type immune response Effects 0.000 description 1
• 210000000173 T-lymphoid precursor cell Anatomy 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
• 239000004473 Threonine Substances 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 108091023040 Transcription factor Proteins 0.000 description 1
• 102000040945 Transcription factor Human genes 0.000 description 1
• ZHAFUINZIZIXFC-UHFFFAOYSA-N [9-(dimethylamino)-10-methylbenzo[a]phenoxazin-5-ylidene]azanium;chloride Chemical compound [Cl-].O1C2=CC(=[NH2+])C3=CC=CC=C3C2=NC2=C1C=C(N(C)C)C(C)=C2 ZHAFUINZIZIXFC-UHFFFAOYSA-N 0.000 description 1
• 150000001241 acetals Chemical class 0.000 description 1
• BOIZHGCLUSQNLD-UHFFFAOYSA-N acetic acid;1h-indole Chemical group CC(O)=O.C1=CC=C2NC=CC2=C1 BOIZHGCLUSQNLD-UHFFFAOYSA-N 0.000 description 1
• INDVHSOTVXHNMA-UHFFFAOYSA-N acetonitrile;1,3-benzothiazole Chemical compound CC#N.C1=CC=C2SC=NC2=C1 INDVHSOTVXHNMA-UHFFFAOYSA-N 0.000 description 1
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
• 239000012346 acetyl chloride Substances 0.000 description 1
• 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 239000008186 active pharmaceutical agent Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 150000001263 acyl chlorides Chemical class 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• 150000007854 aminals Chemical class 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 238000002266 amputation Methods 0.000 description 1
• 230000037005 anaesthesia Effects 0.000 description 1
• 230000003466 anti-cipated effect Effects 0.000 description 1
• 239000000427 antigen Substances 0.000 description 1
• 108091007433 antigens Proteins 0.000 description 1
• 102000036639 antigens Human genes 0.000 description 1
• 208000034615 apoptosis-related disease Diseases 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
• 210000001367 artery Anatomy 0.000 description 1
• 229940072107 ascorbate Drugs 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 230000006472 autoimmune response Effects 0.000 description 1
• 230000005784 autoimmunity Effects 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 229960004365 benzoic acid Drugs 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 230000005540 biological transmission Effects 0.000 description 1
• 230000008499 blood brain barrier function Effects 0.000 description 1
• 210000001218 blood-brain barrier Anatomy 0.000 description 1
• 208000030270 breast disease Diseases 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
• 229910000024 caesium carbonate Inorganic materials 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 210000001168 carotid artery common Anatomy 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 210000003855 cell nucleus Anatomy 0.000 description 1
• 230000004663 cell proliferation Effects 0.000 description 1
• 229940106189 ceramide Drugs 0.000 description 1
• ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
• 239000003610 charcoal Substances 0.000 description 1
• 125000003636 chemical group Chemical group 0.000 description 1
• 239000000460 chlorine Substances 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 210000003483 chromatin Anatomy 0.000 description 1
• 229940114081 cinnamate Drugs 0.000 description 1
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
• 229940001468 citrate Drugs 0.000 description 1
• 229920001436 collagen Polymers 0.000 description 1
• 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000004737 colorimetric analysis Methods 0.000 description 1
• 229940125773 compound 10 Drugs 0.000 description 1
• 229940125844 compound 46 Drugs 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 230000000139 costimulatory effect Effects 0.000 description 1
• 238000007821 culture assay Methods 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 1
• 108010007093 dispase Proteins 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 238000010864 dual luciferase reporter gene assay Methods 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 230000007613 environmental effect Effects 0.000 description 1
• 206010015037 epilepsy Diseases 0.000 description 1
• NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 239000000706 filtrate Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 239000012634 fragment Substances 0.000 description 1
• 239000003205 fragrance Substances 0.000 description 1
• 229940050411 fumarate Drugs 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 229960002598 fumaric acid Drugs 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 1
• 210000003736 gastrointestinal content Anatomy 0.000 description 1
• 238000009650 gentamicin protection assay Methods 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 1
• 229960003132 halothane Drugs 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 239000000833 heterodimer Substances 0.000 description 1
• 239000000710 homodimer Substances 0.000 description 1
• 235000001050 hortel pimenta Nutrition 0.000 description 1
• 229940097277 hygromycin b Drugs 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 238000005462 in vivo assay Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 230000004073 interleukin-2 production Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 125000005990 isobenzothienyl group Chemical group 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• 125000005956 isoquinolyl group Chemical group 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
• 229960003299 ketamine Drugs 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 150000003951 lactams Chemical class 0.000 description 1
• 150000002596 lactones Chemical class 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
• 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 229940098895 maleic acid Drugs 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 210000004962 mammalian cell Anatomy 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 230000004630 mental health Effects 0.000 description 1
• 229960001047 methyl salicylate Drugs 0.000 description 1
• 238000001531 micro-dissection Methods 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 230000002297 mitogenic effect Effects 0.000 description 1
• 230000004660 morphological change Effects 0.000 description 1
• NYIODHFKZFKMSU-UHFFFAOYSA-N n,n-bis(methylamino)ethanamine Chemical compound CCN(NC)NC NYIODHFKZFKMSU-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
• PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
• 230000017074 necrotic cell death Effects 0.000 description 1
• 230000032405 negative regulation of neuron apoptotic process Effects 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 210000004940 nucleus Anatomy 0.000 description 1
• 238000005457 optimization Methods 0.000 description 1
• 239000007968 orange flavor Substances 0.000 description 1
• 210000003463 organelle Anatomy 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 229960005010 orotic acid Drugs 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 230000036542 oxidative stress Effects 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 230000009054 pathological process Effects 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• 229960001412 pentobarbital Drugs 0.000 description 1
• 230000035699 permeability Effects 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 239000010318 polygalacturonic acid Substances 0.000 description 1
• 229920002643 polyglutamic acid Polymers 0.000 description 1
• 230000001242 postsynaptic effect Effects 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 230000003518 presynaptic effect Effects 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 238000003672 processing method Methods 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• 125000006239 protecting group Chemical group 0.000 description 1
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• 238000010791 quenching Methods 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000005493 quinolyl group Chemical group 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 239000011541 reaction mixture Substances 0.000 description 1
• 239000003642 reactive oxygen metabolite Substances 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
• 230000010410 reperfusion Effects 0.000 description 1
• 230000008672 reprogramming Effects 0.000 description 1
• 239000011435 rock Substances 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• 238000003307 slaughter Methods 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 0.000 description 1
• WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
• 239000004299 sodium benzoate Substances 0.000 description 1
• 235000010234 sodium benzoate Nutrition 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 238000000527 sonication Methods 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 210000000225 synapse Anatomy 0.000 description 1
• 230000000946 synaptic effect Effects 0.000 description 1
• 238000001308 synthesis method Methods 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 229920002258 tannic acid Polymers 0.000 description 1
• 235000015523 tannic acid Nutrition 0.000 description 1
• 229940033123 tannic acid Drugs 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 150000003555 thioacetals Chemical class 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
• 230000029069 type 2 immune response Effects 0.000 description 1
• 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 239000003643 water by type Substances 0.000 description 1
• 239000000230 xanthan gum Substances 0.000 description 1
• 229920001285 xanthan gum Polymers 0.000 description 1
• 235000010493 xanthan gum Nutrition 0.000 description 1
• 229940082509 xanthan gum Drugs 0.000 description 1
• 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1